Autoři se zabývají pandemií vyvolanou virem COVID‑19. Snaží se najít příčiny toho, proč tento virus ve světě způsobuje statisíce úmrtí dospělých, ale pro dětskou populaci není vážným problémem. Zatímco nezralá imunita může být pro děti ve věku do pěti let z hlediska ohrožení invazivními bakteriálními infekcemi (Haemophilus influenzae b → epiglottitis acuta) hrozbou, při infekci vyvolané koronaviry může znamenat výhodu. Autoři upozorňují, že C‑reaktivní protein (CRP), respektive jeho izoformy hrají významnou roli v imunitních dějích, a to jak převážně protizánětlivě působící nCRP, tak prozánětlivě účinkující izoforma mCRP.
The authors deal with the pandemic caused by the COVID‑19 virus. They try to find the reasons why this virus causes hundreds of thousands of adult deaths in the world, but it is not a serious problem for the child population. While immature immunity may be a threat to children under 5 years of age in terms of exposure to invasive bacterial infections (Haemophilus influenzae b → epiglottitis acuta), coronavirus infection may be an advantage. The authors point out that CRP or its isoforms play an important role in immune processes, both nCRP predominantly anti‑inflammatory and pro‑inflammatory role as an isoform of mCRP.
- MeSH
- C-reaktivní protein imunologie klasifikace MeSH
- COVID-19 * komplikace MeSH
- dítě MeSH
- imunitní systém MeSH
- lidé MeSH
- pediatrie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- přehledy MeSH
The expression level of acute phase proteins (APPs) mirrors the health status of an individual. In human medicine, C-reactive protein (CRP), and other members of the pentraxin family are of significant relevance for assessing disease severity and prognosis. In chickens, however, which represent the most common livestock species around the world, no such marker has yet gained general acceptance. The aim of this study was therefore, to characterize chicken pentraxin 3 (chPTX3) and to evaluate its applicability as a general marker for inflammatory conditions. The mammalian and chicken PTX3 proteins were predicted to be similar in sequence, domain organization and polymeric structure. Nevertheless, some characteristics like certain sequence sections, which have varied during the evolution of mammals, and species-specific glycosylation patterns, suggest distinct biological functions. ChPTX3 is constitutively expressed in various tissues but, interestingly, could not be found in splenic tissue samples without stimulation. However, upon treatment with lipopolysaccharide (LPS), PTX3 expression in chicken spleens increased to 95-fold within hours. A search for PTX3 reads in various publicly available RNA-seq data sets of chicken spleen and bursa of Fabricius also showed that PTX3 expression increases within days after experimental infection with viral and bacterial pathogens. An experimental infection with avian pathogenic E.coli and qPCR analysis of spleen samples further established a challenge dose-dependent significant up-regulation of chPTX3 in subclinically infected birds of up to over 150-fold as compared to untreated controls. Our results indicate the potential of chPTX3 as an APP marker to monitor inflammatory conditions in poultry flocks.
- MeSH
- biologické markery metabolismus MeSH
- C-reaktivní protein genetika imunologie metabolismus MeSH
- Escherichia coli fyziologie MeSH
- infekce vyvolané Escherichia coli diagnóza MeSH
- kultivované buňky MeSH
- kur domácí imunologie MeSH
- lidé MeSH
- nemoci ptáků diagnóza MeSH
- proteiny akutní fáze genetika imunologie metabolismus MeSH
- ptačí proteiny genetika imunologie metabolismus MeSH
- sekvenční seřazení MeSH
- sérový amyloidový protein genetika imunologie metabolismus MeSH
- upregulace MeSH
- zánět diagnóza MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
BACKGROUND: Biomarkers of intestinal inflammation, such as faecal calprotectin and C-reactive protein, have been recommended for monitoring patients with Crohn's disease, but whether their use in treatment decisions improves outcomes is unknown. We aimed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn's disease who were managed with a tight control algorithm, using clinical symptoms and biomarkers, versus patients managed with a clinical management algorithm. METHODS: CALM was an open-label, randomised, controlled phase 3 study, done in 22 countries at 74 hospitals and outpatient centres, which evaluated adult patients (aged 18-75 years) with active endoscopic Crohn's disease (Crohn's Disease Endoscopic Index of Severity [CDEIS] >6; sum of CDEIS subscores of >6 in one or more segments with ulcers), a Crohn's Disease Activity Index (CDAI) of 150-450 depending on dose of prednisone at baseline, and no previous use of immunomodulators or biologics. Patients were randomly assigned at a 1:1 ratio to tight control or clinical management groups, stratified by smoking status (yes or no), weight (<70 kg or ≥70 kg), and disease duration (≤2 years or >2 years) after 8 weeks of prednisone induction therapy, or earlier if they had active disease. In both groups, treatment was escalated in a stepwise manner, from no treatment, to adalimumab induction followed by adalimumab every other week, adalimumab every week, and lastly to both weekly adalimumab and daily azathioprine. This escalation was based on meeting treatment failure criteria, which differed between groups (tight control group before and after random assignment: faecal calprotectin ≥250 μg/g, C-reactive protein ≥5mg/L, CDAI ≥150, or prednisone use in the previous week; clinical management group before random assignment: CDAI decrease of <70 points compared with baseline or CDAI >200; clinical management group after random assignment: CDAI decrease of <100 points compared with baseline or CDAI ≥200, or prednisone use in the previous week). De-escalation was possible for patients receiving weekly adalimumab and azathioprine or weekly adalimumab alone if failure criteria were not met. The primary endpoint was mucosal healing (CDEIS <4) with absence of deep ulcers 48 weeks after randomisation. Primary and safety analyses were done in the intention-to-treat population. This trial has been completed, and is registered with ClinicalTrials.gov, number NCT01235689. FINDINGS: Between Feb 11, 2011, and Nov 3, 2016, 244 patients (mean disease duration: clinical management group, 0·9 years [SD 1·7]; tight control group, 1·0 year [2·3]) were randomly assigned to monitoring groups (n=122 per group). 29 (24%) patients in the clinical management group and 32 (26%) patients in the tight control group discontinued the study, mostly because of adverse events. A significantly higher proportion of patients in the tight control group achieved the primary endpoint at week 48 (56 [46%] of 122 patients) than in the clinical management group (37 [30%] of 122 patients), with a Cochran-Mantel-Haenszel test-adjusted risk difference of 16·1% (95% CI 3·9-28·3; p=0·010). 105 (86%) of 122 patients in the tight control group and 100 (82%) of 122 patients in the clinical management group reported treatment-emergent adverse events; no treatment-related deaths occurred. The most common adverse events were nausea (21 [17%] of 122 patients), nasopharyngitis (18 [15%]), and headache (18 [15%]) in the tight control group, and worsening Crohn's disease (35 [29%] of 122 patients), arthralgia (19 [16%]), and nasopharyngitis (18 [15%]) in the clinical management group. INTERPRETATION: CALM is the first study to show that timely escalation with an anti-tumour necrosis factor therapy on the basis of clinical symptoms combined with biomarkers in patients with early Crohn's disease results in better clinical and endoscopic outcomes than symptom-driven decisions alone. Future studies should assess the effects of such a strategy on long-term outcomes such as bowel damage, surgeries, hospital admissions, and disability. FUNDING: AbbVie.
- MeSH
- adalimumab terapeutické užití MeSH
- antirevmatika terapeutické užití MeSH
- azathioprin terapeutické užití MeSH
- C-reaktivní protein imunologie MeSH
- Crohnova nemoc farmakoterapie imunologie MeSH
- dospělí MeSH
- glukokortikoidy terapeutické užití MeSH
- indukce remise MeSH
- kombinovaná farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- management nemoci MeSH
- mladiství MeSH
- mladý dospělý MeSH
- prednison terapeutické užití MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
OBJECTIVE: To assess the efficacy and safety of secukinumab in patients with rheumatoid arthritis (RA) who failed to respond to tumour necrosis factor- α (TNF-α) inhibitors. METHOD: This phase III double-blind, double-dummy, placebo-controlled study (NCT01770379) randomized (1:1:1) patients to subcutaneous secukinumab 150 mg, secukinumab 75 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks. American College of Rheumatology (ACR) 20 response at week 24 was the primary endpoint. Secondary outcomes included the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP), Health Assessment Questionnaire Disability Index (HAQ-DI), and ACR50 at week 24. Long-term treatment was planned for 5 years. RESULTS: ACR20 response rates at week 24 for the secukinumab 150 mg and 75 mg groups were not statistically superior to placebo. None of the secondary endpoints was met for either secukinumab dose. Although not statistically significant, compared with placebo, numerically greater differences in least squares mean changes from baseline in HAQ-DI score and numerically higher ACR50 response rates were observed at week 24 in both secukinumab treatment groups. No new or unexpected adverse events were observed in this study compared with the large secukinumab safety database across psoriasis, psoriatic arthritis, ankylosing spondylitis, and other RA studies. CONCLUSIONS: Given that other second-line therapies have demonstrated efficacy in RA patients who failed to respond to TNF-α inhibitors, these findings may suggest that interleukin-17A inhibition with secukinumab does not provide additional benefit to these patients. This study further confirms the well-characterized safety profile of secukinumab.
- MeSH
- antirevmatika terapeutické užití MeSH
- C-reaktivní protein imunologie MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- lidé středního věku MeSH
- lidé MeSH
- monoklonální protilátky terapeutické užití MeSH
- revmatoidní artritida farmakoterapie imunologie patofyziologie MeSH
- senioři MeSH
- terapie neúspěšná MeSH
- TNF-alfa antagonisté a inhibitory MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
Přehledový článek shrnuje možnosti využití stanovení hladin C-reaktivního proteinu nejen v jeho nejčastější indikaci (diferenciální diagnostika akutního zánětu v organismu), ale současně analyzuje nové možnosti jeho využití u onkologických pacientů v rámci prognostických skórovacích systémů, výhody spojení s dalšími biomarkery a také zmiňuje jeho využití jako markeru adaptivní imunitní odpovědi po chemoterapii.
The review article discusses the possibilities of using C-reactive protein levels not only in its most frequent indication (differentialdiagnosis of acute inflammation in the body), but also analyzes new options for its use in oncology patients within prognostic scoringsystems, the benefits of linking with other biomarkers, or seeking its use as a marker of adaptive immune responses after chemotherapy.
- MeSH
- C-reaktivní protein * analýza imunologie MeSH
- diferenciální diagnóza MeSH
- lidé MeSH
- nádorové biomarkery krev MeSH
- nádory ženských pohlavních orgánů krev patologie MeSH
- senioři MeSH
- stupeň nádoru MeSH
- zánět krev MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
- MeSH
- bakteriální infekce MeSH
- C-reaktivní protein * analýza imunologie normy MeSH
- časové faktory MeSH
- hodnocení výsledků pacienta MeSH
- imunologické testy * metody normy přístrojové vybavení využití MeSH
- lidé MeSH
- samovyšetření metody přístrojové vybavení využití MeSH
- virové nemoci MeSH
- vzdělávání pacientů jako téma MeSH
- zánět diagnóza krev MeSH
- zdravotní stav MeSH
- Check Tag
- lidé MeSH
BACKGROUND: Autoantibodies against monomeric C-reactive protein (anti-CRP-Ab) observed in patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN) were suggested to be associated with active LN and a poor response to therapy during short-term follow-up. The aim of this study was to confirm this finding and to investigate the prognostic value of anti-CRP-Ab in patients with LN during long-term follow-up. METHODS: Sera of 57 SLE patients (47 women, 10 men) with biopsy proven LN and 122 healthy individuals were analyzed for the presence of anti-CRP-Ab by in-house ELISA. Anti-CRP-Ab levels were studied in relation to routine laboratory tests, urine analysis, levels of C3, C4, other immunological markers and the overall disease activity as assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The prognostic value of anti-CRP-Ab was tested in a subgroup of 29 newly diagnosed LN patients (median follow-up 5.9 years). Response to therapy at various time points was assessed with respect to baseline anti-CRP-Ab levels. At least partial response in the first/second year of treatment was considered as a "favorable outcome", while non-response, renal flare or end stage renal disease were considered as "unfavorable outcome". RESULTS: Anti-CRP-Ab were only detected in patients with active renal disease and their levels correlated with SLEDAI (rs = 0.165, p = 0.002). The time to response was shorter in patients being anti-CRP-Ab negative at baseline compared to anti-CRP-Ab positive patients, p = 0.037. In the second year of therapy, baseline anti-CRP-Ab positivity was a significant predictor of "unfavorable outcome" (OR [95% CI] = 15.6 [1.2-771]; p = 0.021). The predictive value of "baseline anti-CRP positivity" further increased when combined with "non-response to therapy in the first year". Baseline anti-CRP-Ab positivity was not a predictor of "unfavorable outcome" at the end of follow-up, (OR [95% CI] = 5.5 [0.6-71.1], p = 0.169). CONCLUSIONS: Baseline serum levels of anti-CRP-Ab seem to be a strong risk factor for a composite outcome of non-response, renal flare or end stage renal disease after two years of standard treatment of LN. The response to therapy seems to be delayed in anti-CRP-Ab positive patients.
- MeSH
- autoantigeny imunologie MeSH
- autoprotilátky krev imunologie MeSH
- biologické markery krev MeSH
- C-reaktivní protein imunologie MeSH
- dospělí MeSH
- ELISA MeSH
- lidé MeSH
- následné studie MeSH
- nefritida při lupus erythematodes krev imunologie MeSH
- prognóza MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Recently, we derived "humanized" spontaneously hypertensive rats (SHR-CRP) in which transgenic expression of human CRP induces inflammation, oxidative stress, several features of metabolic syndrome and target organ injury. In addition, we found that rosuvastatin treatment of SHR-CRP transgenic rats can protect against pro-inflammatory effects of human CRP and also reduce cardiac inflammation and oxidative damage. In the current study, we tested the effects of rosuvastatin (5 mg/kg) on kidney injury in SHR-CRP males versus untreated SHR-CRP and SHR controls. All rats were fed a high sucrose diet. In SHR-CRP transgenic rats, treatment with rosuvastatin for 10 weeks, compared to untreated transgenic rats and SHR controls, was associated with significantly reduced systemic inflammation which was accompanied with activation of antioxidative enzymes in the kidney, lower renal fat accumulation, and with amelioration of histopathological changes in the kidney. These findings provide evidence that, in the presence of high CRP levels, rosuvastatin exhibits significant anti-inflammatory, anti-oxidative, and renoprotective effects.
- MeSH
- adipozita účinky léků MeSH
- akutní poškození ledvin farmakoterapie imunologie MeSH
- C-reaktivní protein genetika imunologie MeSH
- hypertenze farmakoterapie imunologie MeSH
- krysa rodu rattus MeSH
- ledviny účinky léků imunologie MeSH
- lidé MeSH
- potkani inbrední SHR MeSH
- potkani transgenní MeSH
- rosuvastatin kalcium terapeutické užití MeSH
- statiny terapeutické užití MeSH
- výsledek terapie MeSH
- zánět farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: Interleukin-20 (IL-20) is implicated in the pathogenesis of rheumatoid arthritis (RA). The efficacy, safety, and tolerability of NNC0109-0012, a selective anti-IL-20 recombinant human monoclonal antibody (mAb), were assessed in patients with active RA who had an inadequate response to methotrexate therapy. METHODS: Sixty-seven patients with RA were enrolled and randomized (2:1) to receive NNC0109-0012 (3 mg/kg per week, subcutaneously) or placebo in a phase IIa, double-blind, 12-week trial with a 13-week followup. The primary end point was change in the Disease Activity Score in 28 joints based on C-reactive protein level (DAS28-CRP) from baseline to week 12. RESULTS: In patients treated with NNC0109-0012, the primary end point, improvement in the DAS28-CRP at week 12, was achieved (estimated difference -0.88; P = 0.02), with significant improvement starting at week 1. A greater response was observed in seropositive patients (estimated difference -1.66; P < 0.001), which was sustained through 13 weeks of followup, whereas no improvement was noted in patients with seronegative RA. A significant proportion of patients with seropositive RA receiving NNC0109-0012, compared to those receiving placebo, achieved treatment responses according to the American College of Rheumatology 20% (ACR20) (59% versus 21%), ACR50 (48% versus 14%), and ACR70 (35% versus 0%) levels of improvement, and showed greater improvements in the Health Assessment Questionnaire disability index (P = 0.047). The most frequent adverse events reported with NNC0109-0012 were injection site reactions and infections (e.g., herpes, nasopharyngitis, respiratory, and urinary). No serious infections or discontinuations associated with NNC0109-0012 were observed. CONCLUSION: In this phase IIa trial, treatment with NNC0109-0012 (anti-IL-20 mAb) was effective in patients with seropositive RA as early as week 1, with further improvements to week 12. No safety or tolerability concerns were identified with weekly NNC0109-0012 administration.
- MeSH
- antirevmatika terapeutické užití MeSH
- autoprotilátky imunologie MeSH
- C-reaktivní protein imunologie MeSH
- cyklické peptidy imunologie MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- herpes simplex chemicky indukované MeSH
- infekce dýchací soustavy chemicky indukované MeSH
- infekce močového ústrojí chemicky indukované MeSH
- interleukiny antagonisté a inhibitory MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- monoklonální protilátky terapeutické užití MeSH
- nazofaryngitida chemicky indukované MeSH
- neutralizující protilátky terapeutické užití MeSH
- revmatoidní artritida farmakoterapie imunologie MeSH
- revmatoidní faktor imunologie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
Cíl studie: Podat přehled současných možností objektivizace tkáňového operačního traumatismu u operací prováděných pro karcinom endometria. Typ studie: Přehledová práce. Název a sídlo pracoviště: Porodnicko-gynekologická klinika LF UP a FN Olomouc. Předmět a metoda studie: Po prostudování současné literatury jsou vybrány a popsány metody určující rozsah tkáňového traumatu s cílem jejich využití při objektivizaci operačního traumatu u různých typů operací pro karcinom endometria. Závěr: Pro objektivní stanovení operačního traumatu zaměřeného na posouzení peroperační zátěže u jednotlivých typů operačních přístupů při chirurgické léčbě karcinomu endometria byly vybrány následující klinické a biochemické markery: VAS, CRP, IL-6, KO, neopterin, kynurenin, retinol a α-tokoferol a citrulin. Uvedené markery budou využity v rámci řešení grantu IGA MZ ČR NT 13 566.
Objective: To review the current possibilities of objective assessment of tissue trauma in surgical treatment of endometrial cancer. Type of study: Review article. Setting: Department of Obstetrics and Gynaecology, Faculty of Medicine and Dentistry, Palacky University in Olomouc. Material and methods: After critical evaluation of relevant contemporary literature, selected methods of the objective estimation of the extent of tissue trauma are presented. The aim of their choice was to find methods objectivly assessing the extent of tissue trauma in connection with using different types of surgical procedures in endometrial cancer treatment. Conclusion: The following clinical and biochemical markers – VAS, KO, CRP, IL-6, neopterin, kynurenin, retinol, α-tocoferol and citrulin seem to be best suitable for the assessment of surgical trauma. These markers should objectivly evaluate the peroperative burden in different types of surgical procedures used for treatment of endometrial cancer. This research is supported by the Czech Grant Agency IGA MZ CR project No. NT 13 566.
- Klíčová slova
- tkáňové trauma, tkáňové operační trauma, markery operačního tramatu, Ca endometria, tissue trauma, markers of surgical trauma,
- MeSH
- alfa-tokoferol diagnostické užití imunologie MeSH
- biologické markery MeSH
- C-reaktivní protein diagnostické užití fyziologie imunologie MeSH
- chirurgie operační * škodlivé účinky MeSH
- citrulin diagnostické užití fyziologie imunologie MeSH
- interleukin-6 diagnostické užití fyziologie imunologie MeSH
- karcinom * chirurgie MeSH
- krevní obraz MeSH
- kynurenin diagnostické užití fyziologie imunologie MeSH
- laparoskopie * škodlivé účinky MeSH
- miniinvazivní chirurgické výkony škodlivé účinky MeSH
- nádory endometria * chirurgie MeSH
- neopterin diagnostické užití fyziologie imunologie MeSH
- peroperační komplikace * MeSH
- rány a poranění komplikace MeSH
- robotika * MeSH
- traumatologie * MeSH
- výsledky a postupy - zhodnocení (zdravotní péče) MeSH
- Check Tag
- ženské pohlaví * MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH